Inclusion Criteria:

1. Female and male outpatients between 18-65 years of age.
2. Meet criteria for revised CDC definition of Chronic Fatigue Syndrome (CFS) (at least 6 months of persistent fatigue that substantially reduces the person's level of activity; 4 or more of the following symptoms that must occur with fatigue in a 6-month period: impaired memory or concentration, sore throat, tender glands, aching or stiff muscles, multijoint pain, new headaches, unrefreshing sleep, and post-exertional fatigue. Medical conditions that may explain the fatigue and psychiatric disorders, including eating disorders, psychotic disorders, bipolar disorder, melancholic depression, and substance abuse within 2 years of the onset of fatigue, are excluded).
3. Provision of written informed consent for participation in the trial.
4. Educational level and degree of understanding such that the patient can communicate intelligibly with the investigator and study staff.
5. Judged to be reliable and agree to keep all appointments for clinic visits, tests, and procedures required by the protocol.

Exclusion Criteria:

1. Current melancholic major depressive disorder, or a previous diagnosis of psychosis, eating disorder, or bipolar disorder.
2. History of substance abuse or dependence within the past year, excluding nicotine and caffeine.
3. A positive urine drug screen for any substance of abuse (may be retested if positive test was for a prescribed medication that was not washed out).
4. Women who are pregnant or breast feeding; women must test negative for pregnancy at Visit 1.
5. Women of childbearing potential who are not using a medically accepted means of contraceptive when engaging in sexual intercourse.
6. Patients who, in the opinion of the investigator, are treatment-refractory or whose response is likely to be compromised by existing or future disability compensation issues.
7. Serious unstable medical illness, including cardiovascular, hepatic, renal, respiratory, or hematologic illness, or other unstable medical or psychiatric conditions that in the opinion of the investigator would compromise participation or would likely lead to hospitalization during the duration of the study. Abnormal TSH concentrations (unless treatment for hypothyroidism has been stable for at least the past 3 months and the patient is clinically euthyroid).
8. Patients who have uncontrolled narrow-angle glaucoma.
9. Patients who have acute liver injury (such as hepatitis) or severe cirrhosis (Child-Pugh Class C).
10. Patients who are judged prior to randomization to be at suicidal risk by the clinical investigator.
11. Treatment with antidepressant medication within 14 days prior to randomization with the exception of fluoxetine, which cannot be used within 30 days prior to randomization. Potential need to use a MAOI during the study or within 2 weeks of discontinuation of study treatment.
12. Patients who have previously taken duloxetine
13. Patients who are taking any excluded medications that cannot be discontinued at Visit 1.
14. Treatment within the last 30 days with a drug that has not received regulatory approval at the time of study entry.
15. Known hypersensitivity to duloxetine or any of the inactive ingredients.